PROJECT SUMMARY/ABSTRACT Acute atherosis (AA) is an inflammatory condition of the uterine spiral arteries within the placental bed that is typically confined to poorly transformed vessels. Although only a subset of women with impaired spiral artery remodeling (ISR) also have AA, the presence of AA is linked to more severe pregnancy complications such as abnormal fetal growth, early onset PE, and a greater risk of maternal and neonatal cardiovascular disease (CVD) in later life. The mechanism of AA is poorly understood, but it has been proposed that women with AA have underlying endothelial dysfunction that is uncovered during the stress of pregnancy. Moreover, subclinical infection by pro-atherogenic bacteria may be a causative factor of AA. Porphyromonas gingivalis (Pg) is a common periodontal pathogen that is implicated in both atherosclerotic disease and obstetric complications associated with placental bed vasculopathies such as PE and fetal growth restriction (FGR). Using a rat periodontitis model, we recently demonstrated that certain Pg strains indeed induce atherosis in the decidua/metrial triangle (placental bed) with ISR. A surprising feature of our study was that Pg infected dams with AA had large for gestational age (LGA) fetuses/pups rather than FGR as reported in the literature. This implies that Pg-induced AA is not a direct cause of FGR as suggested in the literature. A caveat of our study is that we used Sprague-Dawley (SD) rats, which do not develop pro-M1 immune responses to infection during pregnancy. Whereas previous studies that reported Pg-induced FGR used rodent strains that develop pro-M1 immune responses to pathogens. Particularly relevant to our model is that women with PE especially with FGR, exhibit pro-TH1 inflammatory profiles. Based on these features we propose that the host immune response at the maternal-fetal interface is a determinant of fetal growth during Pg-induced ISR and AA. The objective of this application is to use our rodent model to define the Pg-specific and host-specific inflammatory pathways that affect spiral artery remodeling, AA, and influence fetal growth. The central aim of this proposal is to evaluate the impact of preexisting Pg infection on maternal endothelial injury, utero-placental pathology, and its effects on fetal growth in WIS and SD rats. Sub aim 1a will define the subclinical Pg-induced CVD, ISR, and AA phenotype in WIS and SD rats. Sub aim 1b will define the inflammatory profile in WIS and SD rats that is specific to FGR and LGA at gestation days 9 and 18. Relevance to public health: Completion of these studies will provide new insights into 1) how a common pathobiont of the human oral cavity, Pg, promotes obstetric complications, and 2) how the maternal immune response at the maternal-fetal interface, influences fetal growth in the presence of AA.